tbuckley/cabot-search huggingface dataset:
Attention to region: Region-based integration-and-recalibration networks for nuclear cataract classification using AS-OCT images
Authors: Xiaoqing Zhang, Zunjie Xiao, Huazhu Fu, Yan Hu, Jin Yuan, Yanwu Xu, Risa Higashita, Jiang Liu
Journal: Medical Image Analysis (2022)

Nuclear cataract (NC) is a leading eye disease for blindness and vision impairment globally. Accurate and objective NC grading/classification is essential for clinically early intervention and cataract surgery planning. Anterior segment optical coherence tomography (AS-OCT) images are capable of capturing the nucleus region clearly and measuring the opacity of NC quantitatively. Recently, clinical research has suggested that the opacity correlation and repeatability between NC severity levels and the average nucleus density on AS-OCT images is high with the interclass and intraclass analysis. Moreover, clinical research has suggested that opacity distribution is uneven on the nucleus region, indicating that the opacities from different nucleus regions may play different roles in NC diagnosis. Motivated by the clinical priors, this paper proposes a simple yet effective region-based integration-and-recalibration attention (RIR), which integrates multiple feature map region representations and recalibrates the weights of each region via softmax attention adaptively. This region recalibration strategy enables the network to focus on high contribution region representations and suppress less useful ones. We combine the RIR block with the residual block to form a Residual-RIR module, and then a sequence of Residual-RIR modules are stacked to a deep network named region-based integration-and-recalibration network (RIR-Net), to predict NC severity levels automatically. The experiments on a clinical AS-OCT image dataset and two OCT datasets demonstrate that our method outperforms strong baselines and previous state-of-the-art methods. Furthermore, attention weight visualization analysis and ablation studies verify the capability of our RIR-Net for adjusting the relative importance of different regions in feature maps dynamically, agreeing with the clinical research.
Sintilimab combined sorafenib as first-line therapy in patients with advanced hepatocellular carcinoma: A single-arm, single-center, open-label, phase II study.
Authors: Jiabei Wang, Lianxin Liu
Journal: Journal of Clinical Oncology (2022)

e16182 Background: Combining a PD-1 inhibitor with tyrosine kinase inhibitor has achieved a high response rate for advanced HCC (aHCC) in first-line settings. Sorafenib remains the approved first-line choice for aHCC and demonstrates survival benefit, manageable toxicity and high accessibility in china. This study aimed to explore the efficacy and safety of sintilimab (anti-PD-1 antibody) combined sorafenib in patients (pts) with aHCC. Methods: This is a single-arm phase II study (CTR2000031242). Eligible pts with aHCC, BCLC stage C or B (unresectable or not applicable for TACE), Child-Pugh scores≤7 and ECOG PS ≤ 1 received first-line treatment of sintilimab (200mg, iv, D1) every 3 weeks plus sorafenib (400mg, po, BID) until disease progression or unacceptable toxicity. Primary endpoints was objective response rate (ORR, per RECIST 1.1), and secondary endpoints included safety, disease control rate (DCR), progression free survival (PFS), duration of response (DOR) and overall survival (OS). Results: As of January 30, 2022, 12 pts were enrolled (males 11; median age 54.5 yrs [range 46-68]; BCLC A/B/C: 1/6/5; Child-Pugh A/B7: 5/7; HBV infection 11). All pts received at least 1 cycles of treatments with median cycles 3.5 [range 1-17]. Median follow-up was 3 months [range 0.7-15]. 12 pts were evaluable for response, with an ORR of 17 % (95%CI, 0.1%-41.4%) and a DCR of 33 % (95%CI, 2%- 64%). The median PFS was 3.2 months and median OS was not reached. All pts were evaluable for toxicity, and 6 (50.0 %) pts had at least one treatment-related AE (TRAE). TRAEs occurring in≥20% of pts were pruritus (25%). 1 pt had grade 3 TRAEs. Conclusions: The combination of sintilimab and sorafenib showed promising clinical activities with manageable toxicity for first-line treatment of aHCC. Clinical trial information: CTR2000031242.
Size matters: Functional differences of progenitor cell-derived small extracellular vesicle subpopulations in cardiac repair
Authors: S Van De Wakker, J Bauza Martinez, C Rios Arceo, EF Willms, OJ De Jong, W Wu, P Vader, JPG Sluijter
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): ERC EVICARE, Van Herk Foundation Introduction The use of cardiac progenitor cell (CPC)-derived small Extracellular Vesicles (sEVs) has shown great potential to stimulate cardiac repair post myocardial infarction. sEVs are released by cells and play a role in intercellular communication through transfer of their bioactive content, like RNAs and proteins. Increasing evidence indicates that sEVs present a heterogeneous mixture of vesicle populations, depicting different functional aspects, which hampers clinical translation. Studying sEV heterogeneity could provide new insights into contributing therapeutic mechanisms underlying sEV-mediated cardiac repair. Methods CPC-derived sEVs were purified by flow through chromatography followed by size-exclusion chromatography (SEC) and asymmetric flow field flow fractionation (A4F) for fractionation of different sEV-subfractions. Based on the differential expression of common sEV markers, different subpopulations were determined. sEV subpopulations were further characterized using western blot, nanoparticle tracking analysis, bicinchoninic acid protein assay, transmission electron microscopy and mass spectrometry (MS). Functional differences were studied using different cellular assays to determine AKT phosphorylation, wound healing, angiogenesis and proteasome activity. Results SEC or A4F were used to separate distinct subpopulations of CPC-derived sEVs with a different appearance, size and function. MS analysis confirmed the differences in proteomic expression levels of classical sEV markers, as well as annexins, rab proteins, integrins, histones and proteasomal proteins. Furthermore, differences in cellular components linked to their cellular origin were found. Exposure of recipient endothelial cells to sEV subpopulations demonstrated clear functional differences. Additionally, differences in proteolytic activity of the sEV subpopulations were identified. Conclusions SEC and AF4 allow for isolation and in-depth study of the functional heterogeneity of sEVs. In our study, we observed the presence of different subpopulations based on size, with a different composition and biological function. Increased knowledge of sEV heterogeneity will contribute to a better understanding of the mechanisms of action of sEVs and will improve translation to the clinic and potentially an off-the-shelf approach to stimulate cardiac repair.
Psychological mobile app for patients with acute myeloid leukemia (AML): A randomized clinical trial.
Authors: Areej El-Jawahri, Marlise Rachael Luskin, Joseph A. Greer, Mitchell W. Lavoie, Dagny Vaughn, Daniel Yang, Kofi Boateng, Richard Newcomb, Amir Tahmasb Fathi, Gabriela Hobbs, Andrew Mark Brunner, Gregory A. Abel, Richard M. Stone, Daniel J. DeAngelo, Martha Wadleigh, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2022)

12018 Background: Patients with AML experience substantial decline in their quality of life (QOL) and mood during their hospitalization for intensive chemotherapy. Yet, few interventions have been developed to enhance patient-reported outcomes during treatment. Methods: We conducted a randomized trial of a psychological mobile app (DREAMLAND) for patients with a new diagnosis of AML receiving intensive chemotherapy at Massachusetts General Hospital and Dana-Farber Cancer Institute. Patients were randomly assigned to DREAMLAND or usual care. DREAMLAND was tailored to the AML trajectory and included four required modules focused on 1) supportive psychotherapy to help patients deal with the initial shock of diagnosis; 2) psychoeducation to manage illness expectations; 3) psychosocial skill-building to promote effective coping; and 4) self-care. The primary endpoint was feasibility defined as at least 60% of eligible patients enrolling, and 60% of those enrolled completing at least 60% of the required modules. We assessed patient QOL (Functional-Assessment-of-Cancer-Therapy-Leukemia), psychological distress (Hospital-Anxiety-and-Depression-Scale [HADS] and Patient-Health-Questionnaire-9 [PHQ-9]), symptom burden (Edmonton-Symptom-Assessment-Scale), and self-efficacy (Cancer Self-Efficacy Scale) at baseline and day +20 post chemotherapy. We used ANCOVA to assess the effect of DREAMLAND on outcomes. Results: We enrolled 66.7% (60/90) of eligible patients and 62.1% completed ≥ 75% of intervention modules. At day +20 after intensive chemotherapy, patients randomized to DREAMLAND reported improved QOL (132.06 vs. 110.72, P = 0.001), lower anxiety (3.54 vs. 5.64, P = 0.010) and depression (HADS: 4.76 vs. 6.29, P = 0.121; PHQ-9: 4.62 vs. 8.35, P &lt; 0.001) symptoms, and improved symptom burden (24.89 vs. 40.60, P = 0.007) and self-efficacy (151.84 vs. 135.43, P = 0.004) compared to the usual care group. Conclusions: A psychological mobile app for patients newly diagnosed with AML is feasible to integrate during hospitalization for intensive chemotherapy and may improve QOL, mood, symptom burden, and self-efficacy. Clinical trial information: NCT03372291.
Admixture Mapping in African Americans Identifies New Risk Loci for HCV-Related Cirrhosis
Authors: Hyun-seok Kim, Priya B. Shetty, Spiridon Tsavachidis, Jing Dong, Christopher I. Amos, Hashem B. El-Serag, Aaron P. Thrift
Journal: Clinical Gastroenterology and Hepatology (2022)
Impact of PD1 and PDL1 immunotherapy on non-small cell lung cancer outcomes: a systematic review
Authors: Shivani Setur Kanabar, Abhinav Tiwari, Vina Soran, Prashanthan Balendran, Malcolm Price, Alice Margaret Turner
Journal: Thorax (2022)

Introduction Despite comprising many cancer diagnoses, few treatments are suitable for patients with advanced non-small cell lung cancer (aNSCLC). Trials suggest blockade of programmed death 1 (PD1) or its ligand (PDL1) may be effective for these patients. However, this therapy’s impact on outcomes other than survival, and outcomes of patients not in trials, remains largely unknown. Therefore, we compared the effectiveness of PD1 and PDL1 immunotherapy to chemotherapy and placebo across multiple clinical outcomes. Methods Six databases were searched on 12–13 October 2019 for randomised controlled trials (RCTs) and observational studies investigating nivolumab, pembrolizumab, atezolizumab or durvalumab. Study selection was performed independently by two reviewers. Data for overall survival, progression-free survival, adverse effects (AEs) and quality of life (QoL) were descriptively and meta-analysed. Factors impacting treatment outcomes, including PDL1 expression, were explored. The similarity between RCT and observational data was assessed. Results From 5423 search results, 139 full texts and abstracts were included. Immunotherapy was associated with a lower risk of death than both comparators. In RCTs, the incidence of treatment-related AEs was approximately 20% lower among patients using immunotherapy compared with chemotherapy. However, no other consistent benefits were observed. Progression-free survival results were inconsistent. Improvements to QoL varied according to the instrument used; however, QoL was not recorded widely. Survival results were similar between study designs; however, AEs incidence was lower in observational studies. Discussion Among patients with aNSCLC, immunotherapy improved overall survival and incidence of treatment-related AEs compared with chemotherapy. Benefits to progression-free survival and QoL were less consistent. PROSPERO registration number CRD42019153345.
Artificial intelligence (AI)–powered spatial analysis of tumor-infiltrating lymphocytes (TIL) for prediction of response to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC).
Authors: Hee Jin Lee, Soo Yoon Cho, Eun Yoon Cho, Yoojoo Lim, Soo Ick Cho, Wonkyung Jung, Sanghoon Song, Mingu Kang, Jeongun Ryu, Minuk Ma, Seonwook Park, Kyunghyun Paeng, Chan-Young Ock, Sang Yong Song, Gyungyub Gong
Journal: Journal of Clinical Oncology (2022)

595 Background: Stromal TIL are a well-recognized prognostic and predictive biomarker in breast cancer. There is a need for tools assisting visual assessment of TIL, to improve reproducibility as well as for convenience. This study aims to assess the clinical significance of AI-powered spatial TIL analysis in the prediction of pathologic complete response (pCR) after NAC in TNBC patients. Methods: H&amp;E stained slides and clinical outcomes data were obtained from stage I – III TNBC patients treated with NAC in two centers in Korea. For spatial TIL analysis, we used Lunit SCOPE IO, an AI-powered H&amp;E Whole-Slide Image (WSI) analyzer, which identifies and quantifies TIL within the cancer or stroma area. Lunit SCOPE IO was developed with a 13.5 x 109 micrometer2 area and 6.2 x 106 TIL from 17,849 H&amp;E WSI of multiple cancer types, annotated by 104 board-certified pathologists. iTIL score and sTIL score were defined as area occupied by TIL in the intratumoral area (%) and the surrounding stroma (%), respectively. Immune phenotype (IP) of each slide was defined from spatial TIL calculation, as inflamed (high TIL density in tumor area), immune-excluded (high TIL density in stroma), or desert (low TIL density overall). Results: A total of 954 TNBC patients treated from 2006 to 2019 were included in this analysis. pCR (ypT0N0) was confirmed in 261 (27.4%) patients. The neoadjuvant regimens used were mostly anthracycline (97.8%) and taxane (75.1%) -based, with 116 (12.1%) patients receiving additional platinum and 41 (4.3%) patients treated as part of immune checkpoint inhibitor or PARP inhibitor clinical trials. The median iTIL score and sTIL score were 4.3% (IQR 3.2 – 5.8) and 8.1% (IQR 6.3 – 13.4), respectively. The mean iTIL score was significantly higher in patients who achieved pCR after NAC (5.8% vs. 4.5%, p &lt; 0.001), and a similar difference was observed with sTIL score (12.1%.1 vs. 9.4%, p &lt; 0.001). iTIL score was found to remain as an independent predictor of pCR along with cT stage and Ki-67 in the multivariable analysis (adjusted odds ratio 1.211 (95% CI 1.125 – 1.304) per 1 point (%) change in the score, p &lt;0.001). By IP groups, 291 (30.5%) patients were classified as inflamed, 502 (52.6%) as excluded, and 161 (16.9%) as desert phenotype. The patients with inflamed phenotype were more likely to achieve pCR (44.7%) than other phenotypes (19.8%, p &lt; 0.001). Conclusions: AI-powered spatial TIL analysis could assess TIL densities in the cancer area and surrounding stroma of TNBC, and TIL density scores and IP classification could predict pCR after NAC.
QOL-12. Relaxation technique of imagery based story telling reduces manifestation of anxiety in children and adolescents undergoing brain tumor surgery
Authors: Christina Goßler, Tilmann Schweitzer, Jürgen Krauß, Oliver Andres, Stefan Mark Rueckriegel
Journal: Neuro-Oncology (2022)

Abstract Children and adolescents undergoing surgical resection of brain tumors are prone to marked psychologic burden. Especially fear of surgery and its consequences like pain or neurologic sequelae is an important issue. Techniques of relaxation might reduce the intensity of the experienced anxiety and therefore might improve quality of life. In this study, we aimed at determining the effect of a standardized imagery story telling on experienced anxiety as quantified by the questionaire KAT III and cardiac frequency (CF) before and after intervention at two time points (before and after surgery). 12 patients (age: 6-17 years) undergoing brain tumor resection were included in the study. KAT III-scores and CF were determined and compared before and after interventions using a dependend t-test. Mean KAT III-score before first intervention was 0.23 (SD: 0.23), while it was 0.15 (SD: 0.21) after (p = 0.11). Mean KAT III-score before second intervention was 0.11 (SD: 0.13), after: 0.05 (SD: 0.9), p = 0.07. Mean CF before first intervention was 77.1 (SD: 10.3), after: 68,36 (SD: 6.8), p = 0.003. Mean CF before second intervention was 71.67 (SD: 9.57), after: 65 (SD: 8.72), p = 0.003. CF was significantly lower post-interventionally after the first and the second intervention. KAT III-score showed a trend to be lower post-interventionally after the second intervention. Hence, our study points at an efficacy of the deployed relaxation technique of imagery story telling in children and adolescents undergoing brain tumor surgery, although it was limited by a small patient number. Further studies with larger patient numbers and a comparison of randomized intervention vs. non-intervention groups are warranted.
Obesity impairs hypogonadism compensation leading to age-related testosterone decline
Authors: T.LN. Tiraboschi, E.P Miranda, M.T. Novaes, C. Silva, J.C.C. Zambrano, A.P.R. Ribeiro, N.S. Oliveira, M. Pauferro, R.M.C. Pimenta, R.G. Figueiredo, J.M. Bastos-Netto, C.M. Gomes, J Bessa Junior
Journal: European Urology (2022)
Prognostic testing and treatment patterns in Black patients (pts) with chronic lymphocytic leukemia (CLL) from the informCLL prospective, observational registry.
Authors: Jacqueline Claudia Barrientos, Anthony Mato, Jeff Porter Sharman, Danielle M. Brander, Meghan E. Gutierrez, Linda Wu, Sumeet Panjabi, Alex Young, Sandhya Upasani, Maoko Naganuma, Nilanjan Ghosh
Journal: Journal of Clinical Oncology (2022)

e18559 Background: Real-world data on practice patterns in Black pts with CLL are limited. We evaluated treatment (tx) patterns and prognostic biomarker testing in Black pts enrolled in the informCLL registry. Methods: Pts who initiated FDA-approved tx for CLL/SLL (index tx) were enrolled from October 2015 to June 2019. Baseline (BL) characteristics, FISH testing rates, BL factors associated with FISH testing, and patterns of index tx are summarized by line of therapy (LOT; previously untreated [1L] and relapsed/refractory [R/R]). Results: Of 1462 enrolled pts (overall registry population), 106 (7%) were Black (Table). Community-based practices enrolled 87% of Black pts, similar to the overall population (93%). Black pts were predominantly enrolled in the South (69%). Among Black pts, median age was 66 y, 65% had ECOG status ≥1, 64% had Rai stage III-IV, and median time from diagnosis to tx on registry was 40 mo (7 mo for 1L). In the overall population, median age was 71 y, 53% had ECOG status ≥1, 51% had Rai stage III-IV, and median time from diagnosis to tx was 41 mo (19 mo for 1L). FISH testing was performed in 25% of Black pts, similar to the testing rate in the overall population (28%). In a multivariate analysis, BL factors significantly associated with FISH testing were shorter time from initial diagnosis to tx, better ECOG status, earlier LOT (1L), community practice setting, and prior malignancy (p&lt;0.05 for all); race was not a predictive factor. As in the overall population, ibrutinib was the most frequent tx among Black pts in 1L (50%) and R/R (67%), followed by chemoimmunotherapy (CIT; 1L, 43%; R/R, 15%). In 1L pts, tx with ibrutinib generally increased over time (2016, 31%; 2017, 57%; 2018, 63%; 2019, 55%) while CIT use persisted (56%; 36%; 38%; 36%, respectively). In R/R pts, use of ibrutinib decreased over time while CIT remained consistent and tx with other novel agents increased. Conclusions: Black pts with CLL tended to be younger, with worse ECOG status, more advanced disease, and shorter time to 1L therapy than the overall informCLL registry population. While ibrutinib was the most common tx in Black pts, CIT use in 1L remained persistent. Similar to the overall registry population, prognostic testing rates were suboptimal in Black pts. These results highlight the importance of prognostic testing and the need to more closely monitor disease status in Black pts as they will tend to require initial CLL therapy more rapidly than other pts. Clinical trial information: NCT02582879. [Table: see text]
Animal Models of Cardiovascular Complications of Pregnancy
Authors: Zolt Arany, Denise Hilfiker-Kleiner, S. Ananth Karumanchi
Journal: Circulation Research (2022)

Cardiovascular complications of pregnancy have risen substantially over the past decades, and now account for the majority of pregnancy-induced maternal deaths, as well as having substantial long-term consequences on maternal cardiovascular health. The causes and pathophysiology of these complications remain poorly understood, and therapeutic options are limited. Preclinical models represent a crucial tool for understanding human disease. We review here advances made in preclinical models of cardiovascular complications of pregnancy, including preeclampsia and peripartum cardiomyopathy, with a focus on pathological mechanisms elicited by the models and on relevance to human disease.
LINC-06. Prevalence and outcomes of Autoimmune encephalitis in a tertiary hospital in Baguio City, Philippines
Authors: Jaidi Sagay
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Autoimmune Encephalitis is a debilitating neurological disorder that develops as a rapidly progressive encephalopathy, occurring usually less than 6 weeks, caused by brain inflammation. There are limited data on the autoimmune cases in the locality. This study aims to determine the prevalence and outcomes of patients with Autoimmune encephalitis cases admitted in a tertiary hospital in Baguio City, Philippines. METHODOLOGY: This is a descriptive retrospective cross-sectional study that reviewed health records of patients managed as autoimmune encephalitis in a tertiary hospital from January 2015 to December 2020. Descriptive Statistics using frequencies and percentages were employed in the study. RESULTS: A total of 21 patients were included in the study, majority of which were adolescent patients, with male predominance and are residing in rural areas. The most common clinical manifestation presented were fever, behavioral changes, generalized motor seizures, orofacial and limb dyskinesias. EEG revealed abnormal results in 14 patients (66.67%). Majority of patients had normal CSF analysis, while 2 (38.1%) revealed elevated CSF protein levels. Eight patients (38.1%) tested positive for anti-NMDAR titers. Most patients had normal ultrasound and cranial CT Scan (47.62%). The length of stay was more than 2 weeks and majority (80.95%) of patients were discharged improved. CONCLUSION: The prevalence of autoimmune encephalitis is 5/10,000 pediatric population in a span of 6 years which was noted to be increasing over time. The demographic and clinical profile maybe used as predictors of outcome of autoimmune encephalitis, hence, it can help in the management of the said disease.